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“These important grants will provide a strong foundation for expanding research in ME/CFS, and lead to knowledge about the causes and ways to treat people affected by this mysterious, heartbreaking, and debilitating disease,”

Simmaron to Collaborate in Columbia’s Landmark NIH Center of Excellence

Dr. Ian Lipkin and the Center for Infection and Immunity at Columbia University have been awarded one of three NIH grants to produce a collaborative research center dedicated to ME/CFS. Simmaron’s Scientific Advisor Dr. Daniel Peterson is a clinical collaborator on the team.

This collaboration is the culmination of a 6-year partnership between Columbia, Dr. Peterson and Simmaron Research, among others, that have produced 6 peer-reviewed publications that have identified immune changes leading to new profiles of patient subsets.

The total research grant package – $35 million for three research centers and a data center over a 5-year period – is likely the largest single infusion of NIH funding into ME/CFS research ever. The highly competitive NIH process involved 10 grant applications from across the U.S.

Ian Lipkin – Pathogen Hunter

Nobody is better at pathogen research than Ian Lipkin, and no subject is more important than how a seemingly innocuous infection turned into a chronic, often debilitating and life-long illness for many.

If anyone is well-situated to explore that question, it’s Dr. Lipkin. A key innovator in the pathogen field, Dr. Lipkin was the first to show that genetic testing could discover new pathogens to science. Dr. Lipkin invented MassTag PCR, the first panmicrobial microarray, and was the first to use deep sequencing in pathogen discovery.

In 2014 Lipkin’s lab received a $31 million, five year NIH grant to establish The Center for Research in Diagnostics and Discovery (CRDD). Although the CRDD is not specific to any disease, one of its key goals is a subject dear to many ME/CFS patients’ hearts: understanding why infectious agents create enormous problems in some people but not in others. For example, identifying the “host factors” which turn a usually recoverable infection in a person with ME/CFS into a “never-ending flu” will be critical in learning how to turn the clock back in ME/CFS.

More recently Dr. Lipkin’s new method of viral analysis was described as a breakthrough for precision medicine. Acclaimed as one of ten world-changing ideas of 2015 by the Scientific American, the new VirCapSeq-VERT test is able characterize the genetic composition of any virus in any bodily fluid quickly and cheaply “with exquisite sensitivity and accuracy”. Given the heterogeneity probably present in ME/CFS, Dr. Lipkin’s focus on developing tools for precision medicine – which focuses on identifying unique factors in each individual – is probably going to be helpful indeed.

In short, Dr. Lipkin’s extensive research record, his interest in the effects pathogens have on the body, and his ability to keep himself and his lab on the cutting-edge of science made him an obvious choice to host an ME/CFS research center.

“We will leverage every technological platform possible to solve ME/CFS. We will get there.” Ian Lipkin

Lipkin’s goal is a simple one – to come up with treatments as soon as possible. During a telephone conversation, Lipkin abjured the idea of an “ME/CFS research center”; he’s not building a center to research ME/CFS, he said, he’s building a center to find solutions for ME/CFS – hence the name “Center for Solutions for Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (CfS for ME/CFS)”. He anticipated that a variety of treatments are going to be needed for different people.

The new Center has three main aims – understanding how pathogens affect immune functioning and cause disease in ME/CFS, understanding links to the microbiome and host interactions, and developing a mobile app to better understand the symptoms and stressors in this disease.

Samples may be a problem for some but they’re not a stumbling block for Ian Lipkin. He and his colleagues have built a large biobank with the support of the NIH, the Chronic Fatigue Initiative and crowdfunded Microbe Discovery Project that includes feces, saliva and blood. What he hasn’t had is the funding to test them to the extent that he’s wanted to.

Now he has some of the money he needs carry out what amounts to his grand plan to study ME/CFS. Ultimately Lipkin hopes to figure out how an infectious trigger managed to wreak so much havoc on many people with ME/CFS.

Lipkin’s team will be using his VirCapSeq-VERT technology to get a snapshot of all the viruses a person has been exposed to. He’ll be using technology developed using a grant from the Bill and Melinda Gates Foundation to identify the bacteria present. He’ll also be assessing fungi.

Along with immune functioning he’ll be looking at autoantibodies, a hot topic right now. Fluge and Mella are pursuing autoantibodies in their Rituximab work, and autoantibodies appear to play major role in some cases of postural orthostatic intolerance syndrome (POTS) – a condition many people with ME/CFS have. Just last year, a German study Fluge and Mella collaborated in, found autoantibodies to acetylcholine and beta-adrenergic receptors in about 30% of ME/CFS patients. The presence of these antibodies could help explain why Rituximab is helpful in some.

Noting the work Mark Davis of Stanford has done regarding T and B-cell responses, Lipkin said he hoped to work with him to use microarrays to try and determine what those cells are responding to in ME/CFS.

Daniel Peterson, M.D.

We haven’t thought of Lipkin as a metabolomics researcher, but he’s now engaged in no less than three metabolomics projects with Oliver Fiehn of the University of California Davis: a Simmaron Research Foundation cerebrospinal fluid project with Dan Peterson, a blood metabolomics study, and with the new research center, the first ever exercise metabolomics study.

Lipkin described metabolomics as a way to peer inside the body and see that chemicals that result from the body’s functioning. Reduced levels of neurotransmitters, for instance, could mean a balky nervous system, high levels of other factors could be suppressing the immune system, reduced levels of energy building blocks or by-products could reveal an energetic deficit affecting many functions. Metabolomics will also help him determine if the metabolites from the bacteria in our bodies could be affecting immune and central nervous system functioning.

The team will also analyze the metabolites and gene expression before and after exercise tolerance tests and an orthostatic intolerance test called the Lean Test, developed by NASA, which Dr. Bateman and the Bateman-Horne Center began piloting in an ME/CFS study. If metabolism is indeed a key problem in ME/CFS, we can expect the already striking metabolic findings in ME/CFS to get considerably more striking as exercise and standing tests put ME/CFS patients metabolism to the test.

Dana March and Tony Komaroff will also develop a mobile app called myME/CFS that will allow them to track symptoms in response to stressors and treatments. It will allow those with the disease to chart the course of their illness, and will allow clinicians and researchers to use these valuable data for insights. This will supplement work the team will be doing in mining existing databases for subtypes and risk factors.

Lipkin has more projects than he has money to fund them. During a Directors’ meeting at the NIH Lipkin pressed Dr. Koroshetz on the need for more funding for the research centers, but talking to him on the phone he said firmly, “We will get there.” He said his team would leverage every resource he can, and exploit every technological platform possible to solve ME/CFS.

Ian Lipkin, Dr. Peterson and the Simmaron Research Foundation

Dr. Lipkin’s interest in chronic fatigue syndrome (ME/CFS) – and his connection with Dr. Peterson – goes back decades. His first acquaintance with the disease, interestingly enough, came from one of Dr. Peterson’s patients way back in 1984. Dr. Lipkin talked about that and his search for more resources in a 2014 video.

Since Dr. Lipkin re-emerged in the ME/CFS field through the XMRV studies, Dr. Lipkin and the Simmaron Research Foundation have collaborated on several ground-breaking studies. The Lipkin/Hornig blood cytokine study identified, for the first time, evidence of dramatic immune upregulation early in the disease followed by what appears to be an equally dramatic period of immune exhaustion.

Next, Dr. Peterson’s years of experience informed another spinal fluid analysis which, for the first time, identified an “atypical” subset of ME/CFS patients who had dramatically different immune findings. A follow-on cerebral spinal fluid study examining metabolomics and immune factors is underway by Simmaron and Columbia.

Advocate and Messenger

Dr. Lipkin is one of a very few ME/CFS researchers to aggressively advocate for this disease, and he acknowledged the ME/CFS community for its work.

“The pace of research has increased, thanks largely to advocacy by the ME/CFS community and the generous support of the Hutchins Family Foundation. We are grateful to NIH for recognizing the potential of this ME/CFS CRC to capitalize on this momentum, bringing together the very best clinical and scientific talent and technology to do work needed to turn a corner on this disease.” Ian Lipkin, MD

The Lipkin team will also connect with the key players in the digital online media (The Solve ME/CFS Initiative, ME Action and the Microbiome Project) to disseminate the group’s work, engage patients and break up the stigma surrounding ME/CFS.

“One of our goals is to dissolve barriers between scientists, clinicians, individuals with ME/CFS, and advocates. By connecting with the global digital ME/CFS community, we aim to increase the visibility and reduce the stigma of what many have described as an invisible population.” Dana March, assistant professor of Epidemiology at the Mailman School and deputy director and administrator of CfS for ME/CFS.

Simmaron Research is proud of its longstanding collaboration with Columbia, and we congratulate all of the collaborators, patients and advocates who worked hard for years to make this landmark investment by NIH in ME/CFS research centers happen.

Simmaron, Meet CFSAC

Starting this week, Simmaron Research will serve as one of three non-voting organizations on the federal Chronic Fatigue Syndrome Advisory Committee that makes recommendations to the Assistant Secretary of Health and federal health agencies on the unmet needs of ME/CFS patients.

A federal advisory committee on ME/CFS may not seem like a hot topic but there’s no denying that it’s a vitally important one. Even at its current low levels, the federal government funds many times more ME/CFS research than any other entity. Federal decisions affect how this disease is diagnosed, viewed and treated. Given that reach into ME/CFS matters, any committee with the potential to effect federal government action is vital indeed.

Since Simmaron Research is committed to redefining how ME/CFS is understood and treated, it will seek to add its voice to others on CFSAC to urge a stronger federal action plan.

An N of One

CFSAC (Chronic Fatigue Syndrome Advisory Committee) is actually special. Many advisory committees exist in HHS and its agencies, but almost all focus on broad biological issues. CFSAC is one of a select few focused entirely on one disease. Formed when the feds were under attack for misappropriation of CFS funds, CFSAC was meant to give ME/CFS insulation from the prevailing bias in federal agencies, and provide a direct avenue to decision makers at the Department of Health and Human Services.

It hasn’t always worked out that way. CFSAC has provided many strong recommendations to the Secretary or Assistant Secretary of Health over the years, some of which have been acted on, but many of which have not, to the deep frustration of the community. The committee’s potential, though, is great. CFSAC’s twice yearly meetings provide one of the only constant forums for dialog between the ME/CFS community and federal health agencies, and it is a critical window into federal work, as well as a reminder of the extent of patients’ unmet need. It’s strength is its unique blend of government-appointed outside experts, advocates and federal representatives.

CFSAC has had it’s shining moments. Its rejection of Dr. Reeves’s reappointment as CDC ME/CFS chief almost certainly played a role in his ouster when the Obama administration came in. Arguably the most important report in ME/CFS’s history, the Institute of Medicine (IOM) report “Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness“, came out of CFSAC recommendations and was initiated by the committee’s Designated Federal Officer. Similarly, the “NIH Pathways to Prevention” report on ME/CFS research needs, which provided the foundation for the upcoming establishment of the first NIH Research Centers for ME/CFS in over 15 years, emanated from CFSAC recommendations and NIH’s ex-officio to the committee.

A New CFSAC Member (Who Isn’t New to CFSAC)

Robert Miller and patients seek NIH funding at CFSAC, 2010

ME/CFS advocate and Simmaron board member, Courtney Miller, will represent Simmaron Research and the ME/CFS patient community at CFSAC for the next two years. Married to longtime patient Bob Miller, Courtney is an experienced advocate who will continue to push the federal government to increase the resources this disease so desperately needs.

The Millers’ advocacy efforts, which date back decades, include many presentations at CFSAC and participation at ME/CFS meetings and conferences, such as the NIH State of the Knowledge Conference, the FDA Advisory Committee on Ampligen, the NIH Pathways to Prevention Working Group, and the Institute of Medicine Workshop. Over the years, she and Bob have met with numerous high-ranking federal officials, including soliciting a promise from President Obama at a Town Hall meeting which led to a high-ranking official from his administration engaging in ME/CFS matters. Working with many advocates, Courtney has helped prepare pages of recommendations to NIH to inform its renewed research program. Their goal has always been stronger research funding and access to treatments for ME/CFS patients.

A Look to the Future

Simmaron Research believes great opportunity for an impactful federal program on ME/CFS is ahead of us.

The compelling IOM and P2P reports and increasingly prominent ME/CFS research publications (including Simmaron collaborations) marked a turning point in 2015 for the federal government and the disease. Director Francis Collins announced a renewal of NIH’s ME/CFS research program and brought it under the leadership of Dr. Walter Koroshetz, Director of the National Institute for Neurological Diseases and Stroke (NINDS). A comprehensive NIH Intramural Study is underway and new NIH research centers will soon be funded. A reinvigorated community advocacy campaign led by SolveMECFS and MEAction is generating increased Congressional and media scrutiny. The building blocks of a sustained, permanent program to improve federal action on ME/CFS are starting to come together.

Sacramento Millions Missing Rally June 2017

“Given the advances in science and increased recognition of ME/CFS over the last couple of years, I believe we are facing the best opportunity in this disease’s history for a federal response worthy of patients’ crushing unmet need. And yet, we have a long way to go. I hope to work together with advocates to build on the momentum of CFSAC to achieve increasingly higher levels of interaction and engagement with federal agencies responsible for our health. The government’s primary goal has to be finding evidence-based treatments for seriously ill patients.” Courtney Miller

Simmaron hopes to continue the strong advocacy of the patient organizations that served for the last two years on CFSAC and the experts who continue to serve.

CFSAC: The Nuts and Bolts

One of ten advisory committees overseen by the Office of the Assistant Secretary of Health (OASH), CFSAC is tasked with providing “advice and recommendations” to the federal government on everything from federal research efforts to disability to provider information.

CFSAC consists of 13 voting members from the research, healthcare and patient communities, 8 non-voting ex-officio members from branches of the federal government (CDC, NIH, FDA, etc.) and 3 non-voting members from patient organizations. The three non-voting members from patient organizations now include Simmaron Research, The Massachusetts CFIDS/ME & FM Association and ME Action.

CFSAC holds two two-day meetings a year: a webinar-based meeting and a public meeting. The meetings usually contain presentations on ME/CFS from invited experts, patients and caregivers; reports from internal CFSAC groups on topics of interest; reports from the NIH, CDC and other branches of the federal government on their activities; and conclude with recommendations to the Assistant Secretary of Health from CFSAC itself.

Courtney Miller will be presenting on Simmaron’s behalf in the next CFSAC meeting in four days on June 29th from 1:30 to 2:30 pm EST. Check out CFSAC’s agenda and listen to her’s and other’s presentation using this call in number (1-888-788-9429) and Passcode: 4510479

Making Music For ME/CFS

For the second time this month, the loved one of an ME/CFS patient has dedicated talent and sacrifice to raise funding for Simmaron Research and awareness of the disease more broadly.

Michael Jasper met Terry’s husband, Silvestre, 13 years ago and over time the two couples became best friends, even like family to each other but for a while they were a family with a mystery: Terry would mysteriously disappear at times. When the Jaspars were told she had something called “chronic fatigue syndrome” the explanation helped even as it obscured.

Terri Gilmete – in her scooter – advocating for ME/CFS

It wasn’t until Michael and his wife Marie saw a screening of “The Forgotten Plague” earlier this year that they really began to understand what was going on. Terry wasn’t just tired – she was really sick! They’d seen her only on her best days, which unfortunately were few and far between.

“The Forgotten Plague” turned out to be a line of demarcation for them. They’d pounded Terry with questions about the disease after that. They now know the history, they know the neglect, they know the seeds of change that are sprouting now and they wanted to do something for their friend.

Several months later Michael asked for a meeting and when Terry was well enough Michael and his family broke the news: he was resurrecting his music career and wanted to dedicate the song “Beachwalk” to Terry and the ME/CFS community. He’d composed it years before, and when he and his daughter, Marissa, got to work on the album, it was the first song they’d worked on.

Michael told me that he’d played in the greatest garage bands that never made it. Along the way, he’d played and toured around the world with many figures in the music industry. Now as he re-emerged into the music scene he was putting those connections to good use – having them join him on the new album he and his daughter – who, having just graduated from college with a degree in music – were going to release in December. Merging old and new – his old-school R & B and funk roots with her contemporary pop and dance sound – the album will have a unique sound.

Beachwalk’s melody described for him a simple pleasure that few people with ME/CFS could enjoy: a relaxing walk on the beach, the sun overhead, the sand in their toes – a walk that left them relaxed and rejuvenated. Such an easy thing to contemplate for most people but just a dream for Terry and so many others.

For me I heard the keyboards, horn and guitar singing a song of triumph; a song celebrating someone finally making it to their beach after years of effort. It was an uplifting feeling.

Music for Simmaron

It was out of a vision of Terry, their good friend of many years, and others with ME/CFS finally taking their well-deserved walk on the beach, that Michael is donating 50% of the proceeds from the sale of Beachwalk to the Simmaron Research Foundation to help people with ME/CFS.

Please take a walk on the beach with Michael Jaspar, his daughter Marissa and other as they play for Terry Gilmete and others with ME/CFS to support Simmaron. You can find Beachwalk:

Millions Missing Rally & a Song in Sacramento on June 2nd

The problem, of course, is that people with ME/CFS aren’t able to walk far, if at all. They’re largely missing from the rounds of daily life – an absence dramatically evoked by the MillionsMissing rallies featuring ME/CFS supporters and their shoes.

Terry Gilmete and Linda Tannenbaum

This Friday, June 2, patients and loved ones will gather on the steps of the Capitol in Sacramento for a MillionsMissing Rally and a live debut of the Jaspars’ Beachwalk.

The Sacramento Rally featuring Terry Gilmete, Michael Jaspar and others has a story all its own. The woman who organized it, Marilyn Yu, also created “The Forgotten Plague” screening which opened Michael Jaspar’s eyes and got him, his wife and daughter involved. In 2016, Marilyn, who’s had ME/CFS for three years, got West Sacramento, Elk Grove and Sacramento to do proclamations of their own. She’s gotten the Sacramento City buildings lit up in blue for the past 2 years. The Sacramento Convention Marque featured May 12 as ME/CFS Awareness Day. Marilyn also created a virtual run last year in which she raised some money for Simmaron.

On May 18th, a number of California patients including Terry Gilmete and Marilyn Yu met with Senator Glazers and Moorlach to sponsor SCR-40 which proclaimed May 12th ME/CFS Awareness day and the month of May Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Awareness Month in California. Senator Moorlach passionately spoke of his friend’s daughter who’s been disabled from ME/CFS for 18 years.

WHEREAS, ME/CFS has been found by the National Academy of Medicine to be “a serious, chronic, complex, and systemic disease that frequently and dramatically limits the activities of affected patients,” leaving them with a lower quality of life than patients with multiple sclerosis, stroke, renal failure, heart failure, and other chronic diseases; and

WHEREAS, The lack of tracking for ME/CFS by the CDC and the grossly inadequate NIH funding for research based on disease burden have hindered progress in diagnosing and treating ME/CFS, such that there is no FDA-approved treatment for the disease; and

WHEREAS, ME/CFS is a tragic and disabling disease that destroys the lives of many patients and imposes a severe toll on their families, friends, and caretakers;

WHEREAS, The economic impact of ME/CFS in the United States is estimated to be $20 billion to $50 billion per year (CDC February 2016) and likely costs the California economy billions of dollars in health care costs, patient care, lost productivity, and lost tax revenues;

From Australian Rally

The Legislature hereby proclaims May 12, 2017, as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Awareness Day, and declares the month of May 2017, and each May thereafter, as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Awareness Month, to help spread awareness of the disease and the need for increased research funding, and to support individuals living with ME/CFS;…

On June 2nd, Michael Jaspar, Marilyn Yu, Terri Gilmete and others will all be at ME/CFS Millions Missing Rally in Sacramento at the CA State Capitol Steps-south side on June 2 from 11:30-1:30. A shoe exhibit will be on display from 10:30-4. The music will be an inspiration all our own in the ME/CFS community.

Most people in their late 60’s probably aren’t running half marathons. Alex Ribaroff had run them twice before, when he turned 50 and 60, and he swore he would never do a half-marathon again. But here he is, at age 67, three months into his training, on the verge of doing just that.

Tom was perfectly healthy until he came down with infectious mononucleosis at age 16

This time he’s not doing it to celebrate a milestone. He’s doing it to for his son, Tom. Tom was a strapping young man – athletic, academically inclined and outgoing – when he fell prey at 16 to an Epstein-Barr virus (EBV) infection in the UK. Getting exposed to EBV as a child is usually a piece of cake but if you encounter it as an adolescent, it’s another deal indeed; it’s a very common trigger for ME/CFS.

Tom got hit so hard he had to leave school. Two months later, still not well but itching to get back, he returned – only to get hit harder by another bout. That was five years ago. Tom is at University now, he’s hanging on but everything other than academics – sports, exercise, socializing – is out. It’s no way for a young man to get through college.

Tom and his family went through the same experience that so many other sufferers from ME/CFS have – the fruitless search for help – the suggestions to use CBT and graded exercise.

Slowly, Alex and his wife Denise learned more about ME/CFS, the many people affected, the few experts, its marginalization and it’s need for funding. They’ve come to grips with the fact that their young son has a debilitating and chronic illness that many have not recovered from – and they decided to try and do something about it.

They’re raising money to support ME/CFS research. It’s not like they’re experts at this. In fact, they’re complete novices, but their burning commitment to help is pushing them to do things they’ve never done before.

When I asked them why they were stepping out like this, Alex and his wife described the helpless feeling they had watching their young son get sicker and sicker. “You expect your children to be healthy” he said, and if they’re not then “you expect the medical profession to be able to do something about it.” No one should have to experience that feeling around their children.

By chance, a year ago, a friend of the family sent them an article from the Guardian newspaper in the U.K., talking about the research advances being made by Mady Hornig and the Center for Infection and Immunity.

Hornig MD, and Ian Lipkin, a world-renowned pathologist, have taken a special interest in ME/CFS. The blood and spinal fluid studies they’ve done in collaboration with the Simmaron Research Foundation (SRF) and other groups found that ME/CFS patients first exhibit a pattern of high immune activation which is followed by immune exhaustion. Their joint CII/Simmaron Research Foundation cerebral spinal fluid study found a degree of immune dysregulation similar to that found in multiple sclerosis. (An expanded study is underway). Another joint CII/Simmaron Research Foundation study identified a new class of ME/CFS patients (“atypical patients”) who have unusual disease trajectories and test results). Their latest study found dramatic differences in the gut flora which may eventually lead to targeted gut therapies.

A conversation with Hornig led the Ribaroff’s to get in touch with Dr. Peterson and the Simmaron Research Foundation. Only then did they feel that they had found a clinician who understood this illness and might be able to help them.

When they found out how many people’s lives are blighted by the disease, and how many people’s future has been darkened by the cloud of ME/CFS hanging over them, their focus shifted. The fight became about more than for Tom. It became a fight for everyone who has this illness.

So, Alex at age 67 is now lacing up his running shoes for a half-marathon he didn’t ever expect to run again. He’s raising money for two groups – the Simmaron Research Foundation and Columbia University’s Center For Infection and Immunity- that provided them with answers when they desperately needed them.

Alex was appalled by the helpless feeling he and wife had when Tom got sick. Now they’re doing something about that.

They’ve put the call for help far and wide to their friends, many of whom were shocked to hear the healthy, young man they’d known was struggling so much. Jen Brea’s moving “TED talk” – now seen by over 1,200,000 people – proved to be a powerful introduction to a disorder many of them had never heard of. Alex and Denise hope to raise $75,000 – the first $25,000 of which they will match.

The Ribaroffs are getting more involved. They’re going to meet with Dr. Peterson, Dr. Hornig and other luminaries at the London “Invest in ME” conference, to better educate themselves about global advances in research.

But first comes the run. In just two days Alex will put the memories of the last two runs aside and step out onto the track and run – for his son and everyone else with ME/CFS.

Please support Alex and Denise‘s commitment to help their son and many others with your donation to the Simmaron Research Foundation here. (The Simmaron Research Foundation will receive half of the donations raised and will provide the other half to support Ian Lipkin and Mady Hornig in their ME/CFS work at the Center for Infection and Immunity.) PayPal and Credit Cards accepted.

Update: Sixty-seven year old Alex Ribaroff successfully completed the Bermuda Half-Marathon on the 25th of May 🙂

Simmaron recently held a patient update session with its Scientific Advisory Board and key collaborators in Incline Village, Nevada. The event celebrated the Simmaron Research Foundation’s fifth year anniversary. I don’t know if anyone would have predicted five years ago that patients would be hearing from the likes of Mady Hornig, Maureen Hanson, Konstance Knox and Elizabeth Unger but here they were in little Incline Village talking about their work.

CDC Collaboration

The surprise guest at the event was Elizabeth Unger. Dr. Unger was a fitting guest at the Simmaron’s 5th year anniversary meeting; it’s been, after all, just over five years since she took over the helm of CDC’s Chronic Fatigue Syndrome (ME/CFS) program. Who would have thought five years ago that the head of CDC’s CFS program would show up at a Simmaron information meeting.

Certainly not Dr. Peterson. About five years ago I asked him if the CDC had ever shown interest in his work, and he just laughed. His relationship with the CDC was frosty to say the least. That’s not true any longer.

Under Dr. Reeves, the CDC developed a definition in-house that received zero support from researchers (and patients). Under Dr. Unger, the CDC has made ME/CFS experts a core feature of its work, is meeting with patient groups, has worked with CFSAC on its website, and is engaging with patients and experts in its educational materials.

Instead of a stumbling block, Dr. Unger turned out to be a collaborator who’s committed an enormous amount of time, energy and her (limited) budget to learning about ME/CFS doctors and their patients. What a shift that has been.

Dr. Unger threw all the definitions out the window in the multisite ME/CFS expert study. Realizing that doctors, most of whom had decades of experience in this disease, were a better source of what ME/CFS was than any definition, she cleared the decks; anyone the expert doctors believed had ME/CFS, whether they met x or y definition or not, she would study. They were, by default, ME/CFS patients. Dr. Peterson thought it was a brilliant move.

At Dr. Peterson’s invitation, Dr. Unger stayed following a routine site visit to hear the presentations from Simmaron’s Scientific Board and attend the patient gathering. At the patient meeting she had some good news; the first paper from the ME/CFS experts multisite study was finally under review for publication.

It had been a long time coming. Simmaron and Dr. Peterson are already deeply immersed in the greatly expanded second phase of the trial, and had just gotten a contract for the third phase of the study. The study was already slated to continue at least into 2017 and now will continue further.

This now immense study involving over 800 patients and controls will surely supplant the infamous PACE trial as the largest and longest ME/CFS study ever done. With a third phase slated to begin shortly, it’s going to provide an unprecedented look at a very large group of ME/CFS patients, and how they are tested and treated by doctors over time.

Dr. Unger quickly went over a few of the highlights; the greatest heterogeneity, surprisingly, was found within the ME/CFS expert’s sites, not between them. By and large, the practitioners are not seeing different kinds of patients; instead each is seeing a similarly wide variety of patients. How wide? The standard functional tests being done, for instance, indicate that some people with ME/CFS experience high rates of pain while others experience no pain at all.

The constant is that ME/CFS is producing high reductions in vitality and physical functioning but has relatively little effect on mental or emotional functioning. Dr. Unger said the multisite studies will go a long way to helping the public understand how severe a disease ME/CFS is.

Konstance Knox

Konstance Knox, PhD, is collaborating with Simmaron on her insect infection study at Coppe Healthcare. She posited the interesting idea of ME/CFS having a similar trajectory to Lyme Disease. Lyme Disease,she noted, first showed up in pediatrician’s offices in children with arthritis in Old Lyme, Connecticut in the 1970’s. Eventually the children were found to be infected with bacteria carried by ticks.

ME/CFS patients have been showing up in doctor’s offices with unexplained fatigue, post-exertional malaise, pain and debilitating symptoms for years. Could a similar scenario prevail for at least a subset of ME/CFS patients? Knox thinks it might. Her large study, using samples from 300 ME/CFS and healthy controls gathered in the NIH’s XMRV study, is looking for evidence of pathogens that aren’t always tested for in chronic fatigue syndrome (ME/CFS). They include three different kinds of Borrelia bacteria, the Powassan and Dengue viruses, and the most widespread insect borne disease in the U.S., West Nile Virus.

Each demonstrates how rapidly insect borne pathogens can invade a country. Borrelia was identified as the cause of Lyme in 1981, and according to one estimate, is believed to effect 300,000 people a year. West Nile Virus was first found in New York in 1999 and has spread across the country. Now the Zika virus is beginning to touch upon our southern shores in Florida as well.

In Dr. Knox’s mind, the Powassan virus is the big mystery. Carried by the same ticks that cause Lyme disease, Powassan is similar to tick-borne encephalitis virus which has long been shown to cause serious illnesses in Eurasia.

Unlike the Lyme bacteria, which needs the tick to be attached for quite some time for the bacteria to get transmitted, the Powassan virus can be transmitted in just 15 minutes. Knox found that 11% of the 2,000 ticks she studied in Wisconsin carried Lyme disease and 6% carried the Powassan virus. She found 55% of people infected with Lyme disease also were infected with the Powassan virus.

Dr. Knox’s preliminary data of ME/CFS patients with an acute flu-like onset found a low incidence of Lyme disease (3%) but a pretty high incidence (11%) of people who had antibodies which looked like they might be to TBEV; i.e. the Powassan virus. The NIH samples offer an opportunity to study these infections in well characterized patients and controls from multiple clinical sites.

Dr. Mady Hornig

The Hornig/Lipkin team at Columbia’s Center for Infection and Immunity (CII) isn’t just looking at ME/CFS to understand the disease. It’s mining clues from a wide range of disorders – from autism to narcolepsy – to try to understand the disease processes that are occurring. They believe the “omics” revolution – which attempts to understand diseases in terms of their genomics, proteomics, metabolomics (and probably other “omics”) – holds the key to understanding and finding the subsets present in ME/CFS.

Until they get to a cause, Dr. Hornig is unwilling to rule out any possibilities. ME/CFS could be caused by an immune response to a wide range of pathogens (which may be present or not) or to an as yet undiscovered agent. That statement suggested that Dr. Hornig doesn’t consider the earlier CII study which found little or no evidence of pathogens to be the end of the story.

Of course few researchers have looked in the tissues. Dr Chia believes he’s found enteroviruses and Dr. Duffy herpesviruses in the gut tissues of ME/CFS and/or fibromyalgia patients. Hornig and Lipkin have looked in the blood but they’re also raising money to do analyses of the flora in the stool and saliva over time. (Check out the Microbe Discovery Project for more.) Plus, as we’ve seen, a Simmaron/Konstance Knox project is looking for evidence of insect borne illnesses that have not been tested for before.

If pathogens are involved, the heterogeneity in the disease could reflect genetic differences in how each person responded to them, how old the person was when the infection occurred, the state of each person’s microbiome at the time, etc. The take-away message was that different symptoms don’t necessarily mean different diseases.

The CII is doing a lot, but Dr. Hornig started out by focusing on a hot topic these days – metabolomics. The CII team believes that metabolomics may provide the link between what’s happening in the microbiome and the rest of the body. Metabolomics uncovers the breakdown products of metabolism. If a substance, say tryptophan is not being metabolized properly in the gut, it can leave a metabolic signature in the blood that can be picked by metabolomics tests. From the blood it’s apparently a pretty straight shot to the brain.

Marrying gut (microbiome) and blood (metabolomics) data would be the cat’s meow, and it’s begun to happen. Several small studies have been able to link altered gut bacteria to the presence of gut metabolites in the blood. A small Solve ME/CFS Initiative study carried that idea one step forward by adding exercise to the mix. It suggested that exercise could, probably by increasing leaky gut issues, result in increased levels of gut metabolites in the blood.

Dr. Hornig believes that aberrant tryptophan metabolism in the gut could provide a major clue for ME/CFS patients. These metabolic by-products have already been associated with several neurological diseases and are known to cause symptoms similar to those found in chronic fatigue syndrome (ME/CFS). If she finds problems with tryptophan metabolism in the gut and then can pick up their metabolic by products in the patient’s blood she can make a strong case for a gut-brain connection in ME/CFS.

While she was at it, she also noted that these bacteria can affect NAD+ and energy production. To sum up, Dr. Hornig is gathering data on a process that could be affecting cognition, the gut and energy production in ME/CFS.

No Mady Hornig talk it seems is complete without an emotional moment. Every event I’ve seen her at has left her and others in tears at some point, and it happened again. I watched an older gentleman come over and clasp her hands. Five minutes later there they were hugging each other and sobbing away.

Top Poop Crew

Dr. Peterson and Simmaron won the top poop collector award

While on the microbiome she noted, with a smile, that of all the groups they were working with, Simmaron was the best poop collector; Dr. Peterson gathered more stool samples (hundreds of them apparently) from more patients than any other doctor they were working with. (Go Simmaron :))

Maureen Hanson

Maureen Hanson, PhD, presented some interesting news recently when she announced during an SMCI webinar that her small metabolomics had duplicated the Naviaux study’s core finding that ME/CFS was a disorder of reduced metabolism; i.e. it’s a hypometabolic disorder.

That finding helps us understand her Simmaron talk a bit better. Hanson explored the subset question more deeply than anyone I’ve seen before. Chronic fatigue syndrome (ME/CFS), she said, could be a bunch of different diseases, or one core pathology could be driving it.

Whatever it is, the diversity of symptoms found in the disease has produced a credibility problem because diseases which produce lots of symptoms have long been considered “psychosomatic”. The many different triggers ME/CFS and outbreaks has been associated with, and the many different bodily systems it effects, have been confusing as well.

Hanson thought it was intriguing that the symptom presentations seen in different locales appears to be similar! If ME was the result of different agents producing different diseases in different places then the locales should look very different but they don’t. Hanson then fished out a bevy of factors which could affect symptom presentation; the age at which ME/CFS occurred, gender, genetic background, co-infections present, pathogen variations, treatments tried, degree of exercise attempted – all of these could conceivably tweak one disease into producing different symptoms. (Consider what happens to some people who collapse and appear to revert to a different state after overexertion or after using the wrong drug.)

She noted that her mitochondrial DNA study suggested that slight alterations in ME/CFS patients’ mitochondrial DNA could result in different symptoms. That sure presents just the tip of the iceberg with regards to genetics. (Ron Davis and the Open Medicine Foundation will be attempting to marry genetic data and metabolomics in one of their studies.)

Hanson’s microbiome project was powered by a small NIH grant and took place in a Cornell lab famous for its microbiome work. The project was a small one but it made a big splash and was picked up by over 50 media outlets.

The study’s finding – a reduced diversity of bacterial species (about 20% less) similar to that found in two potentially devastating gut diseases (Crohn’s and ulcerative colitis) gave Hanson the opportunity to tell the media again and again that ME/CFS is a real disease. The study also found that ME/CFS patients’ gut bacteria tended to be more dominated by a smaller number of bacteria.

Bacteria of the Ruminococcaceae family – important in fighting inflammation – were significantly reduced in ME/CFS. The representatives of another bacterial family called Enterobacteriaceae – which contains some rather nasty pathogens but hundreds of other species – doubled in ME/CFS patients.

At the genus level, Faecalibacterium prausnitzii, a butyrate bacteria, which produces an anti-inflammatory protein and protects the intestine was reduced in ME/CFS. A similar finding is found in irritable bowel syndrome.

The low butyrate findings in both Hornig and Hanson’s microbiome studies suggest they are both on the right track. That’s actually a big win given how complex (and new) microbiome analysis is, but perhaps it is not surprising given the pedigree of the labs doing the analyses.

As did a Solve ME/CFS Initiative study, Hanson also found evidence that gut materials were leaking into the blood of ME/CFS patients – a process that could spark an inflammatory process that makes its way all the way up to the brain.

[Butyrate – One neurobiologist calls butyric acid – which is produced by butyrate bacteria – “an ancient controller of metabolism and inflammation”. He reports that butyrate is the primary source of energy for the lining of the large intestine. Butyrate is such an effective anti-inflammatory that butyrate enemas (which reportedly smell horrible) and oral supplements are being used to combat inflammatory bowel diseases like Crohn’s and ulcerative colitis. Butyrate also appears to reduce intestinal permeability – which Hornig’s/Lipkin’s and Hanson’s studies suggest many be happening in some people with ME/CFS.

Hanson is a careful researcher and she spoke carefully regarding treatment. She noted that the inability of researchers at this point to clearly determine which gut species are present hampers them from recommending treatments. They can determine which families are present but because bacterial families can contain many different kinds of gut species -some of which have opposite functions – the study’s impact on treatment recommendations is not clear.

Atypical vs Typical Patients – the Peterson Subset

For many years Dr. Peterson has speculated about what he calls typical vs atypical ME/CFS patients. It’s not clear to me what the groups consist of but my sense is that typical ME/CFS patients tend to plateau over time and they tend to have familiar co-morbid disorders such as fibromyalgia, migraine, IBS, etc. Atypical ME/CFS patients, on the other hand, tend to have other serious disorders and/or have really serious cases of ME/CFS. Whitney Dafoe and Corinne Blandino are two examples of atypical patients; Whitney because he’s so ill and Corinne Blandino because she has a strange spinal lesion.

At another event, Mady Hornig talked about the dramatic differences found in the CSF of classical versus atypical patients. Virtually all the immune factors tested were higher in the complex atypical vs the classical patients. In fact, the findings in the two subsets were so different that the atypical patients had to be removed from a study comparing healthy controls and ME/CFS patients. Simmaron and the Center for Infection and Immunity have taken a deeper look at the cerebrospinal fluid in these two types of patients.

I asked Dr. Hornig if she thought the atypical patients had a different disease or were an offshoot of more typical patients? She simply said that she thought that the atypical patients needed to be more closely watched. Later Dr. Peterson suggested, however, that they may be profoundly different biologically.

We should know more about the similarities and differences between these two subsets soon. A Simmaron/CII spinal fluid study comparing the two in greater detail has wrapped up. The metabolomics data from the Ron Davis/Open Medicine Foundation severely ill patient study and the Naviaux study examining more typical ME/CFS patients will give us some guidance as well. Plus, the CDC will be comparing the test results of severely ill patients and healthy controls in the third phase of its multisite study.

A talk with Dr. Peterson found him in a more optimistic frame of mind than I’d seen before. While the promised funding package at the NIH hasn’t shown up yet, he was clearly impressed by the Nath Intramural study, the continuing work of the CDC, and the work Ron Davis is doing at the Open Medicine Foundation.

We didn’t talk about Ampligen and Rituximab but advances with both those drugs may make his job easier. Peterson’s stated that his patients have about a 70% response rate to Ampligen. That high percentage probably reflects two things: Dr. Peterson’s feel for who will respond to the drug, and his ability to dose this drug optimally for each patient.

At the IACFS/ME Conference, Hemispherx Biopharma will report a breakthrough in their understanding of the drug effects in ME/CFS. It appears that they’ve found a way to identify which ME/CFS patients respond to Ampligen – a finding that should help doctors and patients decide whether to try the drug, and make their next clinical trial that much easier. Dr. Patrick of Canada appears to have done the same with Rituximab – a very expensive powerful drug that many doctors are probably leery of trying in their patients without more guidance.

Dr. Peterson will be co-leading a session with Drs. Fluge and Mella on Rituximab and Emerging Treatments, and will be a panelist on a session devoted to diagnosing difficult cases of ME/CFS, and will be highlighting a fellowship opportunity with Simmaron, at the International IACFS/ME Conference at the end of October.

With groundbreaking spinal fluid publications, more collaborative studies lined up, and additional findings on their way to publication, the Simmaron Research Foundation (SRF) has made pivotal contributions to the rising science of ME/CFS in its first five years. The Simmaron Research Foundation is committed to translational research efforts that produce solid gains for patients. With collaborators like these, the next five years promise much.

We have a great story from a Simmaron donor, and we hope you get a kick out of it.

Incline Village, home to Simmaron Research, is also the site of a fantastic 4th of July celebration, with myriad festivities of all kinds for all ages. Fan favorite highlights are the annual the rubber duck races, offered by Incline Village Rotary, where (human) entrants can sponsor a traditional yellow rubber duck for $10 or splurge on a platinum duck for $100. Then, a sea of rubber ducks race to win at a Lake Tahoe beach. The winning “pot” is divided between the Rotary Club for its charitable endeavors, and the duck’s sponsor.

This year’s winning platinum duck (as it happens, lucky duck #13), had been purchased by Dana Rieger. When Dana signed up to participate at the Rotary table, she turned to her husband Steve and said, “my duck is going to win and I’m going to give the money to Simmaron!”

Simmaron’s Lucky Duck!

Sure enough, her duck was victorious, and she contributed the $2200 winnings to support Simmaron’s efforts to scientifically redefine ME/CFS. The Riegers are parents of a housebound ME/CFS son, a grateful patient of Dr. Peterson. The family has been supporters of Simmaron over the last three years.

Simmaron Research is grateful for the ongoing support we have received from the Rieger family and many donors like them, who seek progress and answers for loved ones with ME/CFS. The lucky duck race is one way that Simmaron has become part of the fabric of our community, and we are honored – and amused – at how this donation made its way to world class research!

Ian Lipkin flew to Lake Tahoe this December to fundraise for work he’s doing with the Simmaron Research Foundation. In a talk covering his virus hunting career, the threat of pathogens to humanity, and his work with chronic fatigue syndrome (ME/CFS), he dropped a bombshell: he stated that he believes it’s possible to solve ME/CFS in three to five years.

On that hopeful note, let’s learn more about Dr. Lipkin, his work, and his collaborations with Simmaron.

Dr. Peterson’s Introduction

Lipkin’s Columbia Center for Infection and Immunity (CII) has established close ties with the Simmaron Research Foundation. Only a couple of months before, his chief collaborator, Mady Hornig (and Simmaron Scientific Advisory Board member) had given a talk. Now Ian Lipkin was here.

Dr. Peterson started his introduction of Ian Lipkin by noting that he’d known him since they crossed paths in the 1980’s when Dr. Peterson sent him patients suffering from HIV/AIDS.

Lipkin has changed the ways researchers identify pathogens

Ian Lipkin began a new era in pathogen detection when he became the first researcher to isolate a virus (Borna disease virus) using genetics. He identified the West Nile Virus that had throw New York City into a panic, developed technologies to identify SARS and then hand carried 10,000 test kits to Beijing at the height of the outbreak. He most recently discovered a highly dangerous virus that recently jumped into humans called MERS (Middle Eastern Respiratory Syndrome Coronavirus).

Lipkin has pioneered many technological breakthroughs in finding pathogens including the use of MassTag-PCR, the GreeneChip Diagnostic, and High Throughput Sequencing. His latest breakthrough is the development of a new screening technique that enhances researchers ability to find viruses 10,000 fold.

Ian Lipkin Talks

Who says brilliant scientists can’t be a hoot to listen to as well? Ian Lipkin’s presentation was both enlightening and at times hilarious. Exhibiting a wry sense of humor, Lipkin poked fun at himself and virtually everyone around him.

The last time he was in Lake Tahoe, he said, was in 1984 and he hearkened back to the HIV/AIDS patients Dr. Peterson sent him in the early 1980’s.

“When you come to a fork in the road – take it!”

He stated the guiding principle in the search for pathogens could be summed up by the great Yogi Berra’s adage “When you come to a fork in the road – take it!”.

HIV/AIDS was the beginning of many changes. Even after the medical community knew it was being passed in the blood it still took them 2 1/2 years to find it. (In a Discover interview, Lipkin noted that he ran the first clinic in San Francisco that would treat HIV/AIDS (then called GRID) patients with neurological problems. Note an iconoclastic element to Lipkin that showed up early in his career: he was willing to see patients others wouldn’t. Check out Lipkin’s fascinating story of how HIV/AIDS lead to him to study infectious diseases.)

Lipkin first showed a willingness to support underserved groups early in the HIV/AIDS epidemic

Lipkin then worked on a virus which demonstrated the effects a persistent viral infection can have on the central nervous system.

Next, in another story with possible overtones for chronic fatigue syndrome (ME/CFS), he investigated patients who’d come down with what appeared to be a mysterious psychiatric disorder. It took him two years but using a new method involving genetic cloning he uncovered the Borna disease virus. It was the first virus discovered using genetic means.

The Borna virus discovery was a game-changer for pathogen community. Jump forward thirty years(after it took the medical community almost three years to find HIV, and viruses are being discovered using molecular means every week. The Center for Infection and Immunity itself discovered 700 new viruses from 2009-2015.

Lipkin was aware of and interested in ME/CFS in the eighties but there was no money. In 1999 he and Britta Evangaard found no evidence of the Borna disease virus in ME/CFS. From there we jump forward to 2010 when NIH Director Francis Collins tasked Lipkin to determine if a retrovirus, XMRV, was causing ME/CFS. XMRV turned out to be a laboratory artifact, and the paper was retracted – something Lipkin said was not all that unusual in science. (He emphasized that he and Dr. Peterson were very careful to put out studies that would stand the test of time.)

The XMRV discovery tanked but proved to be a boon for ME/CFS by heightening the attention around it. Lipkin had kept an eye on ME/CFS for years and after being hired by the Chronic Fatigue Initiative to take it on, he was back in a big way.

In the next portion of his talk he turned to viruses and humans.

Viruses and Humans

How are most viruses getting into humans? From animals. After it’s jump from primates to humans, HIV is, of course, the most familiar example, but viruses are also escaping from bats, birds, pigs, rodents, insects and even camels into humans.

A sea change in the viral field occurred in 1999 when a mosquito-borne virus – the West Nile Virus – had the audacity to attack the residents of the New York City. Lipkin shifted his work from the West to East coasts to search for the virus and ultimately identified it. As the outbreak spread, it got the attention of Senator Joesph Lieberman who sponsored the first big initiative to learn how viruses spread from animals to humans. Politicians, Lipkin noted, can be important allies.

Most pathogens have yet to be identified by humans.

New York City may be an ideal transit stop for new viruses. Twenty-one million passengers traveling to and from 72 countries pass through New York city airports every year. Animal products including bushmeat – all potentially contaminated with nasty viruses – pour into New York City regularly.

Many more viruses are undiscovered than have been discovered. A survey of one species of bats found fifty-five viruses, fifty of which were new to science. Lipkin estimated 320,000 viruses were still unknown and they’re bumping up against humans all the time. Lipkin next demonstrated how quickly they can jump from animals into humans.

Bats – Called to investigate an ill Saudi Arabian man (with four wives), he uncovered a new virus called MERS (Middle East Respiratory Syndrome) similar to those found in bats. (Asked if there were any bats in the area, he was told no. The next video showed bats flying every which way in the area :)). If the bats weren’t biting the humans, though, how was the bat virus jumping into people?

Lipkin found MERS was present in about 75% of the camels in the country. Further research indicated that MERS jumped into camels in the 1990’s, and then rapidly escaped into humans around 2010.

Since its escape into humans around 2010 MERS has spread to 26 countries.

MERS is not particularly easy to transmit but once it gets transmitted, watch out. Death rates are high. It took just one Saudi Arabian to spread MERS to South Korea this year where it killed several dozen people, put several thousand others into quarantine and basically threw the country into a panic. Schools were closed, tourists stopped coming, and parts of the economy slumped as South Korea fought off the virus. It has since been found in 26 countries. It’s the kind of virus that keeps public health officials up at night.

It’s not surprising that Lipkin is wary of pathogens. He noted that he rarely shakes hands but darting a glance at Dr. Peterson said he’d made an exception that evening.

(If you haven’t seen Steven Soderbergh film “Contagion” and can handle apocalyptic scenario’s you might want to give it a try. Lipkin consulted extensively on the movie which involved a worst-case scenario of a virus wiping out much of humanity. The film was praised for its scientific accuracy. (Spoiler alert – we do survive in the end :)).

Ticks – Coming closer to home Lipkin believes chronic Lyme patients who are not recovering from antibiotics may have gotten another infection from the ticks. He found that over 70% of the Ixodes scapularis ticks associated with Lyme disease carried at least one pathogen and 30% carried more than one in New York. Last year he identified a rhabdovirus (Long Island tick rhabdovirus) new not just to ticks but to science itself. A small survey suggested that 15% of residents may carry antibodies to the virus.

Rats– Lipkin’s study of New York City’s second most common resident – rats – revealed they carried an amazing array of pathogens including Escherichia coli, Clostridium difficile, and Salmonella enterica, Bartonella spp., Streptobacillus moniliformis, Leptospira interrogans, and Seoul hantavirus.

In one of his many asides (did you know he loves Sinatra?) Lipkin referred to the hamburger and French fries lunch that he and Peterson usually have. (“Do as we say not as we do” he said). How does Lipkin reportedly like his meat? “Burn it” he tells the waiter. The man is taking no chances – he knows too much.

Infection and Disease

The timing of an infection is just one of many factors that determine the effects it will have.

A pathogen is just one of the players, however, in a vast swirl of factors which ultimately determines whether one is going to have a chronic illness. Timing, for instance, is a key factor.

If you expose a mouse to a pathogen at one stage of pregnancy, it’ll stop moving around its cage. If you expose the same mouse to the same pathogen later in pregnancy, it will run round and around its cage unceasingly.

A large autism study underscored the complex role timing plays in humans. The 120,000 person autism birth cohort study found that if a mother comes down with a fever after the first trimester, her chances of giving birth to a son with autism go up three-fold. If she treats the fever with acetaminophen, her chances of giving birth to an autistic child drop significantly. If she takes acetaminophen for any other problem than a fever, her risk of giving birth to an autistic child goes up again.

Three to Five Years – An ME/CFS Timeline

How does all this relate to ME/CFS? Likpin cited the findings of their work to date.

The suspected pathogens don’t appear to be the problem (the CII is reportedly looking further at herpesviruses.)

Preliminary evidence suggests that levels “X” and “Y” metabolites and, at least, one immune protein are significantly altered in ME/CFS. (Lipkin embargoed this information pending publication of the paper. One of them is a shocker.)

Lipkin emphasized, though, that ME/CFS is not a one-size fits all disease. For instance, it’s possible that fungi may be a problem for some patients. That’s an intriguing idea given the recent fungi funding in Alzheimer’s disease published in Nature.

Lipkin’s timeline for solving ME/CFS given enough resources – a mere three to five years.

Then Lipkin made his bold declaration “We’re going to solve this in three to five years”. It came with a significant proviso “provided the resources are made available” but indicated that he believes ME/CFS is a mystery that can be cracked fairly quickly. That sounds really fast, but Lipkin’s time-frame is not that far off from Ronald Davis’s 5-10 year time-frame (provided he gets the resources as well.) (or Dr. Montoya’s).

These eminent researchers believe that given the technology present today we could understand ME/CFS fairly quickly – if enough resources were brought to bear. Lipkin pointed to a slate of researchers in his lab working on ME/CFS to signify the major shift he’s seen happen in just the last couple of years. He said “I couldn’t have gotten them five years ago”.

He highlighted two places the patient community can make an impact:

Funding Pilot Studies – The community can fund pilot studies which can be turned into big grants

Advocacy – Lipkin is a savvy researcher. He knows how the NIH works, and once again he emphasized the need for the ME/CFS community to push harder legislatively – to talk to their representatives in the House of Representatives, in particular – and get them to push the NIH for more funding.

Lipkin’s Bucket List

Ian Lipkin has clearly developed a special relationship with ME/CFS, Dr. Peterson, the Simmaron Research Institute. He hadn’t been in the Lake Tahoe area for decades, yet he and two of his assistants had flown across the country to support the Simmaron Research Institute’s spinal fluid work. He was even shaking hands.

Lipkin’s Bucket List contains two items: solving ME/CFS is one of them.

I shook my head – not for the first time – about Ian Lipkin. How had we gotten so lucky? Lipkin oversees the work of 65 researchers in the U.S. and 150 more across the globe. The New York Times reported that on any given day his lab had 140 viral research projects underway. The head of the National Institute of Allergy and Infectious Disease, Anthony Fauci said, “Lipkin really stands out from the crowd.”

Yet, here he was in the Lake Tahoe area in mid-December exhorting the audience to support an important Simmaron study that he believed needed funding.

What had driven the “The World’s Most Celebrated Virus Hunter” to take on our disease? I asked his assistants. They told me that Ian Lipkin wants to do two things more than anything else before he retires: he wants to solve ME/CFS, and he wants to solve autism. We’re on his bucket list.

That floored me even more (:)) so I asked – but, but…..doesn’t he care what other people think about this neglected disease? That question left them almost gasping for breath. After they had been able to calm down, they assured me: no Ian Lipkin doesn’t care.

The Simmaron Research Foundation’s Next Spinal Fluid Study

Lipkin was at the event to support the Simmaron Research Institute’s next spinal fluid study. The results of the first one – the most extensive spinal fluid study ever done in ME/CFS – were eye-opening. Using Dr. Peterson’s suggestion to separate atypical from typical ME/CFS patients, and focusing on patients with a longer duration illness, they’d found evidence of an immune dysregulation almost equal to that found in MS. The difference was that instead of being raised, the cytokine levels were reduced in ME/CFS.

That finding surely left a big smile on Lipkin’s and Hornig’s faces. Earlier they’d found evidence of a profound reduction in immune functioning in the blood of later-duration ME/CFS patients. Now a similar reduction was showing up in their spinal fluid. These unprecedented findings suggested they were uncovering system-wide problems.

No wonder Lipkin was eager to begin a new and larger spinal fluid study: it’s part of achieving his bucket list.

Triple Your Support! – Between now and Dec 31 triple your support for Ian Lipkin’s work with the Simmaron Research Foundation (SRF). A generous donor is offering to match $2 for every $1 donated before Dec 31. The funds will support the SRF’s collaborations with Drs. Ian Lipkin and Mady Hornig at Columbia University.

In a recent Simmaron Tea event, Simmaron’s research collaborators talked about their work to propel discovery in our disease. In Part 2 of our summary, we review Dr. Konstance Knox’s presentation on her collaboration to identify insect-borne pathogens in ME/CFS patients.

Dr. Knox, CEO of Coppe Healthcare Solutions, is a longtime collaborator of Simmaron Research and Dr. Daniel Peterson. A contributor to Simmaron’s spinal fluid studies, she has done years of viral testing and research in patients with ME/CFS and other diseases.

From malaria to dengue fever to Lyme disease, “vector-borne” (primarily mosquito and tick-borne) illnesses are among the more difficult challenges facing the medical community. While they are often associated with developing countries, people in the U.S. are not immune from them. Over 20 insect-borne illnesses occur in the U.S. and more are emerging. A new tick-borne virus (Heartland Virus) was recently identified in the Midwest and Eastern U.S. and the dangerous tick-borne Pawossan virus was recently found in the eastern U.S. The first case of West Nile Virus in the Western Hemisphere was identified in New York in 1999. Five years later it was found in every state of the Union.

Many pathogens have been associated with ME/CFS but no one has looked at insect borne pathogens until now.

We know that infectious onset of chronic fatigue syndrome (ME/CFS) commonly occurs. We know it can be triggered by many different types of infections (Epstein-Barr virus, parvovirus, Giardia, SARS, hepatitis, etc.).

No study, however, has examined the extent of insect triggered illness or looked for regional clusters of such illnesses in chronic fatigue syndrome – until now.

Simmaron Research and Dr. Knox were awarded residual samples from the NIH XMRV study to comprehensively assess the incidence of insect-borne illnesses in ME/CFS patients across the U.S. Dr. Konstance Knox will lead the first study allowed to use the rigorously collected and characterized samples from the XMRV study.

The study builds on historical associations with ME/CFS that have been bypassed in recent years.

History Repeating Itself?

Insect-borne pathogens by their nature tend to form clusters of illness, and chronic fatigue syndrome, of course, first became well-known when clusters popped up in Incline Village/Lake Tahoe, Lyndonville and other cities in the early 1980’s. Dr. Knox reported that since 1934 at least 12 clusters have been identified in the U.S. including six in the Lake Tahoe region alone.

Could your “flu” have come from a mosquito?

Over the past 20 years there’s been little focus on clusters. From the Norwegian Giardia and Canadian SARS to the Ebolavirus outbreaks, however, every significant infectious outbreak has left behind a cluster of ME/CFS-like patients.

This study will look for clusters of regional insect-borne illnesses in ME/CFS patients in the U.S. It is driven by the hypothesis that for some people the “flu” they never got over was not caused by some innocuous cold bug but resulted from a mosquito or tick bite.

Comprehensiveness is a keyword for this study. Now only will it involve hundreds of ME/CFS patients from across the U.S., it will also examine almost all possible insect-borne illnesses found in the U.S. including some that are rarely studied. Studies of this size and scope have rarely been done in ME/CFS. The pathogens tested for include:

Coxiella burnetii – associated with cattle/goats/sheep – spread through dust – across the U.S.

Mosquito-borne Pathogens

West Nile Virus (WNV) – across the U.S.

Dengue Virus (DENV) – southeastern U.S./Texas

Eastern Equine Encephalitis Virus (EEEV) – eastern U.S.

Western Equine Encephalitis Virus (WEEV) – west of the Mississippi

Louis Encephalitis Virus (SLEV) – eastern and central U.S.

California Encephalitis Virus (CEV) – California

La Crosse Virus (LCV) – California

Possibly High Misdiagnosis Rates

Dr. Knox believes misdiagnosis rates of these infections could be high. Some are poorly studied and most doctors don’t know about many of them, anyway. Plus unless severe symptoms are present many are rarely tested for . Sudden seizures or blindness may get you tested for West Nile virus, for instance, but more moderate flu-like symptoms it often produces probably will not.

Lyme disease is endemic in several parts of the U.S.

Post-infectious fatigue states following insect-borne infections appear to be common. Over 50% of people with an active West Nile Virus infection still experienced fatigue, cognitive problems, headaches and muscle weakness eighteen months later. Dengue fever, which has re-emerged in the southeastern United States is known to leave behind an ME/CFS-like condition in some patients. Descriptions of virtually all these infections note the “long-term sequelae”; i.e. the long term effects they can leave behind.

Resolving a Medical Mystery?

Plus, a virus like tick-borne encephalitis virus (TBEV) could hold a clue to controversy that’s roiled the medical profession. Different groups assert that Lyme disease is either a) a relatively rare disease that responds well to antibiotics or b) a common disease that often does not respond to antibiotics and often persists in a chronic state.

Ticked Off? Simmaron is doing the research.

But what if they’re both looking in the wrong place? What if that tick bite transmitted a different infection along with the Borrelia – an infection that is resistant to antibiotics? Could the chronic Lyme disease patients are suffering from be a different, undiagnosed tick-borne illness?

Konstance Knox believes a good candidate may be tick-borne encephalitis virus (TBEV). TBEV is common in Europe and Asia but has been inadequately studied in the U.S. It can produce fatigue that can persist for years and it can be transmitted quickly. People who pluck off a tick before it’s been on them for 24 hours may be relieved that it hasn’t transmitted Borrelia, but TBEV– which is almost never tested for in the U.S. – can be transmitted in fifteen minutes.

Dr. Knox believes she will find a much greater prevalence of exposure to insect borne infections than anyone expects at this point. She hopes this will be the first of many studies examining these illnesses.

Associating ME/CFS with an increased prevalence of insect borne infections would, of course, further legitimize the disease, but the most intriguing impact of the study may be the recognition that some people have undiagnosed but treatable insect borne illnesses.

Resolving a Medical Catch-22

Patients with chronic Lyme disease and those with ME/CFS both suffer from a medical catch-22. If antibiotics don’t return people with Lyme disease to health it’s assumed they have psychological problems. On the flip side, if test results from patients with ME/CFS don’t indicate a recognized disease is present, then their illness must be in their heads as well.

Maybe, just maybe, an infection triggered by a recognized (or unrecognized) pathogen set disturbed the immune systems of both sets of chronically ill patients.

The Simmaron Research Institute believes research holds the answers patients need. This study is the first step. Join Simmaron’s quest for answers.

The Simmaron Research Foundation is out to redefine ME/CFS scientifically. In an recent event called A Simmaron Tea, collaborators talked with patients about their recent work to propel discovery in our disease. Part 1 of our summary will review Dr. Mady Hornig’s presentation, including some early results from Columbia’s ongoing gut studies. Part 2 will summarize Dr. Konstance Knox’s study of mosquito and tick-borne pathogens in ME/CFS patients. Stay tuned!

Simmaron has collaborated with Dr. Hornig on half a dozen studies unfolding the immuological anomalies in ME/CFS. A doctor-scientist by training, she is Associate Professor of Epidemiology and Director of Translational Research at Columbia University’s Mailman School of Public Health.Simmaron’s collaborations with Columbia on spinal fluid studies mark our signature contribution to ME/CFS research. Simmaron is continuing this research by funding a second phase of this work to compare metabolomics and proteomics in ME/CFS and MS patients.

Mady Hornig

“We now know that the same changes to the immune system that we recently reported in the blood of people with ME/CFS with long-standing disease are also present in the central nervous system,” Dr. Hornig

In her presentation, Dr. Hornig first reviewed the recent finding from the Chronic Fatigue Initiative-funded study run by the Columbia team: massive immune up regulation in short duration ME/CFS patients and immune down regulation in longer duration ME/CFS patients. The same immune factors, interestingly enough, that were upregulated early in the illness were squashed later in the illness. One key viral fighter called IFN-y that was hugely important in early ME/CFS but significantly down regulated in later ME/CFS pointed an arrow at a process called “immune exhaustion”.

Immune Exhaustion

The blood and spinal fluid findings matched

The first cerebrospinal fluid study using Dr. Peterson’s carefully collated samples found a similar pattern of immune system down regulation. That study (supported by CFI and Evans Foundation) included only longer duration patients. These two studies – the first to find similar issues in these two different compartments of the body – suggested that the immune system had taken a system wide punch to the gut.

What could cause this kind of immune exhaustion? Dr. Hornig stated it’s usually associated with chronic infections. In a scenario reminiscent of the wired and tired problem in ME/CFS, the immune system gets revved up, stays revved up and ultimately crashes.

That nice concurrence between immune findings in the spinal fluid and in the blood was encouraging, and the group is digging deeper into those CSF samples. Thus far a factor called cortisol binding globulin (CBG) has popped up in protein analyses. This intriguing factor which facilitates the transport of cortisol in the blood, has shown up in chronic fatigue syndrome before and families with certain polymorphisms in their CBG genes have increased fatigue and low blood pressure.

The Peterson Subsets

Earlier, Dr. Hornig noted Dr. Peterson’s exceptional foresight at collecting cerebrospinal fluid samples over many years and his skill at characterizing them. Now she appeared almost dumbfounded at his ability to pluck out subsets in his patients. At Dr. Peterson’s urging, the Columbia team examined the cerebrospinal fluid of what he called “classical” ME/CFS patients and “complex atypical” patients. Dr. Peterson has been talking about the “classical” set of ME/CFS patients vs other types of patients for years, but this was the first time his intuition was put to the test.

Finding subsets was crucial to the success of both studies

The classical patients typically present with infectious onset while ME/CFS in the atypical patients has been associated with post transfusion illness, cancers and other factors. No one before has suggested or attempted to determine if these patients differ biologically.

Dr. Peterson’s intuition that they would be different biologically proved to be correct. Columbia found dramatic differences in the CSF of classical versus atypical patients. Virtually all the immune factors tested were higher in the complex atypical vs the classical patients. The researchers are taking a deeper look at the cerebrospinal fluid in these two types of patients.

The findings also demonstrates how vital it is to tease out subsets. Without breaking patients up into early and longer duration subsets the findings of the CFI’s big immune study would have been negative. Similarly, without excluding Peterson’s subset of atypical patients, the cerebral spinal fluid study findings would have been insignificant. Given the size, expense and prominence of the CFI blood study, in particular, the negative results would have provided a significant impetus for the field to move away from the immune system.

Instead, there is now great interest in immune alterations in ME/CFS. The inability to ferret out biologically important subsets has undoubtedly smothered potentially important findings in ME/CFS in the past. In a short period of time the CFI investigators and Dr. Peterson have added two factors ME/CFS researchers need to consider in their studies: duration of illness and classical vs non-classical patients.

This is an example of “translational medicine” – going from the bench (lab) to the bedside (clinic) and vice-versa – at its best. It can only occur when researchers interact closely with practitioners they trust and vice-versa.

The Gut Work

Mady Hornig believes the gut may hold answers to ME/CFS. The preliminary gut results suggest she may be right.

Columbia’s Center for Infection and Immunity has completed the testing of samples from 50 patients and 50 healthy controls started in the CFI study and extended in an NIH-funded study to analyze ME/CFS microbiome. They are completing analysis of the samples now.

They’re finding evidence of significant changes in the gut flora of ME/CFS patients vs healthy controls. For one, altered levels of butyrate producing bacteria have been found in the ME/CFS patients. Noting that similar differences have been found in autoimmune diseases, Dr. Hornig proposed that an autoimmune process may be fueling the symptoms in a subset of patients.

Another finding suggests substantial serotonin dysregulation may be present in ME/CFS. (Most of the serotonin in our body is found in our gut.) Dr. Hornig described serotonin as a major immune regulator. Thus far they’ve found that serotonin is more likely to be undetectable in shorter duration patients than longer duration patients, and those reduced serotonin levels are associated with increased immune activity including a very significant increase in IFN-Y – an important antiviral factor.

Tryptophan is metabolized to either serotonin or kynurenine. If serotonin levels are low, the levels of kynurenine are likely high. Plentiful serotonin results in feelings of well-being, emotional resilience, and immune balance. High levels of kynurenine, on the other hand, have been associated with a host of neurological and neuropsychiatric disorders. Dr. Hornig has called the kynurenine pathway her favorite pathway because it’s been implicated in so many diseases.

The low serotonin findings in ME/CFS were apparently significant enough for Columbia to begin developing new tests to more accurately assess the presence of kynurenine metabolites. It appears that they’ve been successful in doing that, and we can expect more fine-tuned analyses of the role that pathway plays in ME/CFS.

In discussion afterward the presentation, Dr. Hornig said she was struggling a bit how to relay ideas of low resilience to stress in ME/CFS – some of which low serotonin levels could play a role in – without ruffling feathers. She’s certainly not advocating the SNRI’s or other antidepressants in ME/CFS. In fact, she noted that she was sure ME/CFS patients were amongst the “treatment resistant depression” patients she’d seen when working as a psychiatrist early in her career.

The fix for the serotonin problem – if it is validated in a subset of ME/CFS patients – will clearly come from another direction. A recent review article suggested using the gut flora to affect serotonin-based brain disorders and that is probably the track Dr. Hornig will take. She said she is especially keen to look at the effects of nutraceuticals, probiotics and fecal transplants in ME/CFS.

Dr. Hornig is clearly intellectually excited by her work, but one thing that happened during her presentation indicated her strong emotional connection to it as well. The presentation of a small quilt to her from ME/CFS patients strongly affected her and left her having to momentarily gather herself emotionally. It was a surprisingly moving moment.

Dr. Hornig sounded confident about the direction of their research and stated that they were very much looking forward to what the next few years will bring. She said she was cautiously optimistic that the IOM and P2P reports, the positive immune study, plus the signs that the National Institute of Neurological Disorders and Stroke (NINDS) may be interested in taking ME/CFS on, indicate that a turnaround for ME/CFS funding is in store.

Help Simmaron continue to fund this pivotal work, as we seek to deepen immune findings in ME/CFS and turn them into potential treatments.

Everyone’s Nightmare

It was a nightmarish situation. Struck down by ME/CFS at the age of eight after a series of staph/herpes infections and infectious mononucleosis, the Spearing’s formerly healthy and energetic daughter, Stephanie, was soon confined to her bed.

Then it got worse. Much worse. As Stephanie’s illness progressed, severe sensory problems left her unable to tolerate bright light, sounds, smells and touch. Migratory nerve and abdominal pain left her in severe pain much of the time. Dysautonomia and muscle weakness left her unable to walk. Food sensitivities and gut problems left her unable to tolerate many foods and her weight dropped precipitously. The UK health authorities were – surprise, surprise – no help at all. They didn’t even attempt to be polite in their denials.

Improvement

Stephanie has improved tremendously but is still far from being able to lead a normal life

It was a tragic story that could have easily lead to an even more tragic ending but Stephanie’s move out of the damp UK into the colder but drier climate and more ME friendly health system in Canada helped Rest and more rest, dietary changes, probiotics and immune supplements produced progress.

Seven years later Stephanie is still weak but she no longer experiences the severe sensory problems and pain she once did. She’s not in school but no longer needs her wheelchair and is able to go on walks. Stephanie’s reduced suffering is a great relief to her parents but they want their entire daughter back.

Riding for ME/CFS Research

They want real relief. They want mounds of research. They want their daughter well and they don’t want anyone else to go through what Stephanie and they went through. The awful nights. The walking on tiptoes in order not to cause their daughter – huddled in her bed upstairs – pain from too much noise. The ugly comments from the medical authorities.

Everyone is affected by these severe illnesses. Some give up in the face of the opposition but Peter Spearing has just gotten more determined. In three days in his Ride For ME/CFS Research Peter is riding 100 kilometers in Tour de l’Île de Montréal cycling event to raise funds for the Simmaron Research Foundation. He’s going to ride full out – as hard as he can.

The Institute’s collaborative efforts with top researchers and Dr. Peterson’s years of experience drew the Spearmans to the Simmaron Research Institute

When asked why they choose the Simmaron Research Institute Stephanie’s mother Suzy emphasized Dr. Peterson’s years of experience, and the close ties the Institute has forged with important research efforts across the globe. One of the first articles they read about ME/CFS, she noted, involved Dr. Peterson’s efforts in the Incline Village outbreak over thirty years ago.

Created in 2012, the Simmaron Research Institute is dedicated to scientifically redefining how ME/CFS is studied and treated. It’s dedicated to giving people like Stephanie options. To breaking up the ignorance that is causing so many people to be cruelly treated. To producing an environment in which ME/CFS is given the resources that other chronic illnesses are.

The Institute is currently participating in and/or funding work on

The gut microbiome

Tick, mosquito borne and other pathogens

Determining subsets and defining ME/CFS

Epidemiology including the long term effects of ME/CFS

A genomic analysis of immune cell functioning

The cause of the natural killer cell dysfunction

The extent of severe T-cell abnormalities found

Autoimmunity, non-Hodgkin’s lymphoma and cancer prevalence

Ampligen’s effectiveness in treating ME/CFS

Spearheading efforts to make immune tests a standard part of diagnostic protocols

Collaborating with Columbia University to train future doctors how to treat ME/CFS

The Simmaron Research Institute is dedicated to scientifically redefining ME/CFS

Peter, Suzanne and Stephanie request that you support Peter’s efforts to bolster ME/CFS research by donating to the Simmaron Research Institute here. Everyone, young and old, deserves a shot at a normal, healthy life. (Please reference Stephanie Spearing in the dedication box provided).